Two differential mechanisms of automaticity in diseased human atrial fibers.

The ionic mechanisms of automaticity in spontaneously active preparations (n = 38) from "diseased" human atria were investigated. The cycle length (CL) of the automatic action potential (AAP) ranged from 0.6 to 4.5 s (mean +/- S.D.: 2.0 +/- 1.0 s). The AAP from preparations obtained from non-digitalized patients (group 1, n = 29) showed various CLs, in that 16 patients had a CL longer than 2.0 s (slow-type AAP) while in tissues from the other 13 patients, the CL was 2.0 s or less (fast-type AAP). On the other hand, all preparations obtained from the digitalized patients prior to cardiac surgery (group 2, n = 9) had the fast-type AAP (CL less than or equal to 2.0 s). The slow-type AAP was accelerated and changed to the fast one after application of ouabain (1 microM) or by perfusing with 50% [Na+]o Tyrode solution. Ryanodine (1 microM), a specific inhibitor of calcium release from the sarcoplasmic reticulum (SR), markedly lengthened the CL of fast-type AAP, without affecting the slow-type AAP. In contrast, caffeine (15 mM) shortened the CL of the slow-type AAP and remarkably lengthened the CL of the fast-type AAP, as is the case in ryanodine. The rate of slow-type AAP was enhanced with an increase in [Ca2+]o and depressed with a decrease in [Ca2+]o or with application of diltiazem, a Ca2+ channel blocker. The slow-type AAP was changed to the fast-type AAP by stretching the preparation by about 20%. In vitro preparations excised from patients with dilated atria revealed a shorter CL of AAPs. We conclude that in "diseased" human atrial preparations, the ionic mechanism responsible for generation of slow- and fast-type automaticity differs. Slow automaticity (CL greater than 2.0 s) perhaps relates to activation of the slow inward Ca2+ current, while the fast-type automaticity (CL less than or equal to 2.0 s) is linked to cyclic increases in [Ca2+]i.